Informed Consent Form (ICF) Template Guide for Clinical Trials

Across FDA Bioresearch Monitoring Program (BIMO) inspections, informed consent deficiencies appear among common inspectional observations across clinical investigator and sponsor-investigator programs. FDA conducted 1,073 BIMO inspections in FY2023, and informed consent failures were documented across multiple inspection categories ^[1]. Specific enforcement examples illustrate the range of failures: a June 2025 warning letter cited an investigator for failing to use the IRB-required consent form addendum, leaving subjects enrolled without proper consent documentation ^[17]; a February 2026 warning letter cited the collection of optional aqueous humor samples from a subject who had refused consent for that procedure twice ^[2]. These are not edge cases. They trace back to inadequate ICF template infrastructure, poor version tracking, and sites that treat the consent form as a one-time checkbox rather than a process requiring ongoing management.

This guide covers what every ICF template must contain, how the regulatory framework from 21 CFR Part 50 through ICH E6(R3) shapes those requirements, where templates typically fail inspection, and what a compliant, well-constructed ICF looks like in practice.

Why the ICF Is More Than a Signature Page

The informed consent form is frequently treated as a procedural endpoint, the document a subject signs before enrollment begins. That framing is incorrect, and it is the source of many downstream problems.

As FDA guidance for IRBs, clinical investigators, and sponsors makes explicit, the informed consent process is an ongoing exchange of information throughout a subject's participation in a clinical trial and does not end after the consent form is signed ^[3]. The ICF is a record of what was communicated, a reference document subjects are meant to take home and consult, and a living document that must be updated when new safety information emerges. The signed form documents voluntary agreement, but the process it reflects must be continuous.

This distinction matters operationally. Sites that treat the ICF as a one-time checkbox create compliance risk: when a protocol amendment changes the risk profile of the study, those sites may not initiate re-consent. When new safety findings emerge mid-trial, they may not update the form and re-present it to enrolled subjects. The ICF template itself should be designed to make these obligations visible, not just fulfill minimum element requirements at study startup.

The Regulatory Framework: What Governs ICF Content

Three regulatory layers govern what must appear in every ICF for FDA-regulated clinical investigations.

21 CFR Part 50 (FDA)

FDA's primary human subject protection regulation for clinical investigations is codified at 21 CFR Part 50. The general requirement, set out at 21 CFR 50.20, states that investigators must seek legally effective informed consent from each human subject, and that the circumstances under which consent is sought must minimize the possibility of coercion or undue influence ^[4]. The consent process must give subjects sufficient opportunity to consider whether to participate before signing.

The specific content requirements appear at 21 CFR 50.25, which enumerates eight basic elements and, when appropriate, six additional elements of informed consent ^[5]. A separate requirement at 21 CFR 50.25(c) mandates a ClinicalTrials.gov statement for applicable drug and device trials. Both lists are discussed in detail below. Documentation requirements are at 21 CFR 50.27, which specifies that consent must be documented with a written form approved by the IRB and signed by the subject or legally authorized representative ^[6].

ICH E6(R3) (GCP)

ICH E6(R3), finalized as a Step 4 document in January 2025 and effective in the EU as of July 23, 2025, restructures the GCP guidelines and updates expectations for informed consent ^[7]. Section 2.8.5 of E6(R3) specifies that the consent process should be conducted by the investigator or other investigator site staff adequately trained and delegated by the investigator, in accordance with applicable regulatory requirements ^[8]. The broader E6(R3) framework introduces a risk-proportionate approach across trial operations, including continuing review. This has practical implications for ICF versioning and re-consent workflows: oversight of the consent process should be proportionate to participant risk, not a flat administrative cadence.

45 CFR Part 46 (Common Rule, DHHS)

For federally funded research not covered exclusively by FDA regulations, the revised Common Rule at 45 CFR 46.116 applies. The 2018 revision to 45 CFR 46.116 added a requirement that consent documents begin with a concise key information section presenting the facts most likely to assist prospective subjects in deciding whether to participate ^[9]. FDA has proposed adding identical language to 21 CFR 50.20 through a notice of proposed rulemaking ^[10]. Sponsors and sites developing ICF templates for multi-site trials often build for this key information section regardless of whether the applicable FDA rule has been formally adopted, since IRBs increasingly expect it.

Required ICF Elements: The Complete Framework

Basic Elements (21 CFR 50.25(a))

FDA regulations at 21 CFR 50.25(a) enumerate eight basic elements that must be provided to each subject in every FDA-regulated clinical investigation ^[5]. These are binding requirements, not recommendations.

1. Statement that the study involves research. The ICF must state explicitly that the subject is being asked to participate in a research study. It must explain the purposes of the research, the expected duration of participation, the procedures that will be followed, and identify which procedures are experimental.

2. Foreseeable risks or discomforts. A description of all reasonably foreseeable risks and discomforts to the subject must be included. This section requires meaningful detail; a generic statement that "risks are unknown" is not sufficient where risks have been characterized in the Investigator's Brochure.

3. Benefits. A description of benefits to the subject or to others that may reasonably be expected from the research. Note that benefits must be reasonable and not overstated. The form cannot include promises of therapeutic benefit from an investigational product without evidentiary support.

4. Alternative procedures or treatments. Disclosure of appropriate alternative procedures or courses of treatment, if any, that might be advantageous to the subject. This element is particularly important in therapeutic trials where standard-of-care alternatives exist.

5. Confidentiality of records. A statement describing the extent to which confidentiality of records identifying the subject will be maintained, and that notes the possibility that FDA may inspect the records ^[5]. HIPAA authorization is often bundled into the ICF or provided as a separate authorization document; the applicable state law governing medical record privacy also applies.

6. Compensation and treatment for injury. Where more than minimal risk is involved, the ICF must explain whether any compensation or medical treatment is available if the subject experiences injury, and where to obtain further information.

7. Contact information. The form must provide whom to contact for answers to pertinent questions about the research and the subject's rights, and whom to contact in the event of a research-related injury.

8. Voluntary participation. A statement that participation is voluntary, that refusal to participate will involve no penalty or loss of benefits to which the subject is entitled, and that the subject may discontinue participation at any time without penalty.

Additional Elements (21 CFR 50.25(b))

Beyond the eight basic elements, 21 CFR 50.25(b) lists six additional elements that must be included "when appropriate." Sponsors and IRBs must evaluate each study to determine which apply. The six are enumerated in the current regulation as follows ^[5]:

• A statement that the treatment or procedure may involve currently unforeseeable risks to the subject (or to the embryo or fetus, if the subject is or may become pregnant)
• Anticipated circumstances under which the investigator may terminate participation without the subject's consent
• Any additional costs to the subject that may result from participation in the research
• The consequences of a subject's decision to withdraw from the research and procedures for orderly termination
• A statement that significant new findings developed during the course of the research which may relate to the subject's willingness to continue participation will be provided to the subject
• The approximate number of subjects involved in the study

Multi-Framework Considerations: Common Rule and Additional Disclosures

Trials that are both FDA-regulated and federally funded, or that are governed by the revised Common Rule at 45 CFR 46.116, carry additional disclosure requirements that go beyond the six FDA additional elements. The 2018 Common Rule revision added one new basic element and eight new additional element categories ^[15]. The new basic element at 45 CFR 46.116(b)(9) requires, for research collecting identifiable biospecimens, a statement about whether those biospecimens may be used in future research after identifiers are removed. Three frequently relevant additional elements are the commercial profit statement (45 CFR 46.116(c)(7)), the clinically relevant research results disclosure (45 CFR 46.116(c)(8)), and the whole genome sequencing disclosure (45 CFR 46.116(c)(9)). These elements are in 45 CFR 46.116, not in FDA's 21 CFR 50.25, and the distinction matters: sponsors must identify which regulatory framework governs each study and ensure the template draws from the correct source. Multi-site trials governed by both frameworks require templates that satisfy both sets of requirements.

The Key Information Section

Under the framework FDA has proposed to align with the revised Common Rule, ICF templates are increasingly built with a key information section at the front presenting the facts most important for a prospective subject's decision to participate ^[10]. This section is not simply a summary of all 21 CFR 50.25(a) elements. A joint OHRP and FDA draft guidance on key information, published in March 2024, specifies a focused presentation of what is most likely to assist the subject, rather than a restatement of every required element ^[9]. In practice, the key information section typically covers: what the study is testing, why the subject is being asked to participate, the main procedures involved, the primary risks, whether there are alternatives, and that participation is voluntary.

A well-drafted key information section should aim for plain language accessible to the study's target population. FDA guidance frames the readability requirement as language "understandable to the subject or their legally authorized representative" per 21 CFR 50.20 ^[4]; the commonly cited eighth-grade reading level is a widely used best-practice benchmark applied by medical writers and IRBs, not a specific regulatory standard in FDA regulations.

Building the ICF Template: Section-by-Section Structure

A compliant ICF template follows a logical narrative arc. The goal is a document that a subject with no background in clinical research can read, understand, and use to make a genuine decision. The following structure reflects current best practices and ICH E6(R3) expectations.

Title Page and Identification Block

A controlled ICF template should be identifiable on its face: study title or protocol number, sponsor name, investigational site, IRB-assigned version number and date, and the name of the principal investigator. Version control is not optional. During inspections, FDA has cited sites for failure to obtain an IRB-required consent addendum before enrollment, and consent documentation failures can trace back to inadequate version management and failure to track IRB approval notifications ^[17].

Key Information (Summary) Section

Placed before detailed study information, this section presents in plain language the five to seven most important facts a participant needs. Regulatory guidance recommends using defined sections or visual separation to distinguish the key information from the full body of the form ^[9].

Study Purpose and Background

This section answers one question for the subject: why does this study exist? The explanation should describe what is being investigated, why it matters, and what the sponsor hopes to learn. Technical language should be avoided or immediately defined. FDA guidance is clear that consent documents must avoid language that creates false impressions of benefit or that minimizes risk ^[3].

Procedures

All study procedures must be described, with experimental procedures clearly identified per 21 CFR 50.25(a)(1) ^[5]. Duration of participation, visit schedule, and any randomization must be explained in terms the subject can understand. If the study involves a placebo arm, that must be disclosed and the probability of assignment to placebo stated. Where a study includes optional sub-studies such as genomic sampling, biospecimen banking, imaging substudies, or long-term follow-up, each optional component requires a separately tracked consent element; subjects who decline optional procedures must not be treated as having consented by virtue of signing the main ICF.

Risks and Discomforts

This section requires the most careful calibration. Risks must be described in sufficient detail to be meaningful, but the form should not be so exhaustive as to obscure the primary risk signals. FDA guidance calls for a presentation that distinguishes between common low-severity side effects and serious or potentially irreversible risks ^[3]. All reasonably foreseeable risks based on nonclinical and clinical data in the IB must be reflected here; this section should be reconciled against the current IB version during each ICF update cycle.

Potential Benefits

Benefits must be framed accurately. Many Phase I and early Phase II ICFs cannot promise therapeutic benefit, and the form must say so. The distinction between benefits to the subject and benefits to society or to future patients must be drawn clearly.

Alternatives

This section must identify what standard-of-care treatment options the subject would be forgoing, or declining, by enrolling. It should not create the impression that participation is the only path forward.

Confidentiality and Data Use

Subjects must be informed of how their data will be used, who will have access, how long it will be retained, and that FDA may inspect records. If the trial uses an electronic data capture system, data monitoring committee, or third-party laboratory, the scope of data sharing should be disclosed. For trials governed by the revised Common Rule, the new basic element at 45 CFR 46.116(b)(9) requires a statement about future use of identifiable biospecimens; the commercial profit statement falls under 45 CFR 46.116(c)(7) as an additional element ^[15]. Sponsors developing templates for dual-framework trials should verify which specific sub-provisions apply and attribute them correctly.

Compensation and Injury

Compensation for participation, if any, must be disclosed and described in terms the IRB has approved as non-coercive ^[3]. For studies involving more than minimal risk, the form must explain whether any compensation or medical treatment is available if the subject is injured, and what it covers.

Voluntary Participation and Withdrawal

The statement of voluntariness and the right to withdraw without penalty is required under 21 CFR 50.25(a)(8) ^[5]. The form must also explain any consequences of withdrawal relevant to the subject (such as whether data already collected will be retained and used) and the procedure for orderly withdrawal.

Contact Information

Two categories of contacts are required: a contact for study-related questions and potential benefits or risks, and a separate contact for questions about the subject's rights as a research participant, typically an IRB contact ^[5].

Signature and Date Block

FDA regulations at 21 CFR 50.27 require a written consent document signed by the subject or legally authorized representative ^[6]. The date of signing must be documented. Where a legally authorized representative signs, the relationship should be recorded. The person obtaining consent, if different from the PI, should also sign and date the form, confirming that the consent discussion occurred.

Special Populations: Legally Authorized Representatives, Pediatric Subjects, and Assent

When a prospective subject lacks the capacity to provide legally effective informed consent, consent must be obtained from a legally authorized representative (LAR) whose authority is recognized under applicable state or local law ^[4]. The ICF template should include a LAR signature block where LAR consent is anticipated, along with space to document the representative's relationship to the subject. Note that who qualifies as an LAR varies by state; templates for multi-site trials should include a reference to applicable local law rather than a fixed definition.

For pediatric trials, parents or guardians provide permission rather than consent; the ICF is correspondingly titled as a "parental permission form" in many IRB-approved templates. Separately, FDA regulations at 21 CFR 50.55 specifically require that the IRB determine whether adequate provisions are made for soliciting assent from children capable of providing it, taking into account their age, maturity, and psychological state ^[16]. Assent documents are shorter, written in age-appropriate language, and reviewed as separate IRB-approved materials. Templates for pediatric studies should include provisions for both parental permission and age-appropriate assent, with a clear process for re-assent as the child approaches legal majority during a long-term trial.

Re-Consent: When the ICF Must Be Updated and Re-Executed

FDA's informed consent guidance and regulatory framework create a clear ongoing obligation around re-consent. When new information arises during a trial, the sponsor and investigator are responsible for assessing whether that information could affect a subject's willingness to continue participating ^[3]. If the assessment determines that re-consent is required, by the IRB, by applicable regulations, or by the protocol, then the updated ICF must be re-presented and re-executed with currently enrolled subjects. This is not automatic for every protocol change: the operative question is whether the new information is material to an ongoing participant's decision-making.

Triggers that typically require assessment, and in most cases will require re-consent include:

Substantive protocol amendments. An amendment that changes the study procedures in ways that affect participant risk, duration of participation, or the experimental nature of what subjects have agreed to undergo generally requires an ICF update and an IRB determination of whether re-consent is needed for enrolled subjects. Not every administrative amendment rises to this threshold, and IRBs typically make that determination. Where the IRB directs that enrolled subjects must be re-consented, sites must complete that process and document it before those subjects continue participating ^[3],[7].

New safety findings. 21 CFR 50.25(b)(5) requires that the ICF include a commitment to inform subjects of significant new findings that may relate to their willingness to continue ^[5]. When such findings emerge, sponsors must assess whether re-consent is warranted and coordinate with the IRB on timing and process. The vehicle for communicating new safety information is often an updated ICF, though some IRBs accept a formal notification letter where the nature and magnitude of the finding is limited.

Interim safety data. A safety signal from a data safety monitoring board, unblinding of an interim safety analysis, or significant findings from concurrent studies involving the same investigational product may require assessment for re-consent.

Regulatory authority requests. FDA and other health authorities may require amended consent language as a condition of study continuation. Those directives create a clear re-consent obligation.

The process for re-consent, when required, must be documented with the same rigor as initial consent: date of discussion, subject signature, and where applicable, the signature of the person who conducted the re-consent discussion.

eConsent: Regulatory Basis and Implementation Considerations

In December 2016, FDA finalized guidance on the use of electronic informed consent (eConsent), developed jointly with OHRP ^[11]. The guidance defines eConsent as the use of electronic systems and processes that may employ multiple electronic media, including text, graphics, audio, video, and interactive websites, to convey study information and obtain and document consent ^[11]. Critically, eConsent does not waive or modify any of the required elements under 21 CFR 50.25. All elements must still be present; the electronic format governs how they are presented and how the signature is captured, not what the document must contain.

From an implementation standpoint, eConsent systems used in FDA-regulated clinical investigations must comply with 21 CFR Part 11, as applicable, which governs electronic records and electronic signatures ^[11]. This means the system must be validated, access-controlled, audit-trailed, and capable of producing IRB-compliant records. The FDA guidance specifies that subjects must be provided the opportunity to have questions answered by a qualified person before signing ^[11].

ICH E6(R3) Annex 2, which addresses non-traditional trial elements including pragmatic designs, decentralized trials, and real-world data sources, was adopted by ICH on June 3, 2026, completing Step 4 ^[12]. The Annex covers additional GCP considerations for trials using decentralized elements, real-world data, and pragmatic designs. Sponsors planning non-traditional or hybrid trials should consult the final Annex 2 document for GCP requirements on remote consent, digital health technology use, and data traceability in non-traditional settings.

Regulatory and Documentation Considerations

IRB Review and Approval

No ICF template should be used at a clinical site without prior IRB approval. The IRB reviews both the content of the consent document and the process by which consent will be obtained ^[13]. ICH E6(R3) Section 1 retains and updates IRB/IEC responsibility requirements, including expanded documentation review covering the informed consent process and assent, and introduces a risk-proportionate approach to continuing review in place of a fixed annual cycle ^[8]. Note that FDA regulations retain a separate continuing review requirement: 21 CFR 56.109(f) specifies that an IRB shall conduct continuing review at intervals appropriate to the degree of risk, but not less than once per year ^[18]. The ICF version approved by the IRB must match the version in use at the site; failure to implement all IRB-required consent materials before enrollment has appeared in FDA warning letters ^[17].

Language and Readability

FDA guidance is consistent: informed consent documents must be written in language understandable to the subject or their representative, as set out at 21 CFR 50.20 ^[4]. A commonly applied best-practice benchmark is an eighth-grade reading level, used by medical writers and IRBs to gauge plain-language compliance; this is a widely accepted operational standard, not a specific regulatory requirement in FDA rules. Readability may be adjusted for a highly educated patient population, but the underlying obligation remains the same. If a subject population includes non-English speakers, translations must be prepared, and the use of a short-form consent document, as described at 21 CFR 50.27(b)(2), may be appropriate ^[6]. The short form is a brief written statement that the required elements have been presented orally, with a witness present.

Prohibited Language

21 CFR 50.20 states that no informed consent, whether oral or written, may include any exculpatory language through which the subject or their representative is made to waive or appear to waive any legal rights, or releases the investigator, sponsor, institution, or its agents from liability for negligence ^[4]. FDA and OHRP's joint guidance on exculpatory language characterizes this as any wording that has the general effect of freeing or appearing to free an individual or entity from malpractice, negligence, blame, fault, or guilt ^[3]. The prohibition applies regardless of how the language is framed. Some sponsors include broadly worded release provisions in consent templates without recognizing they violate this requirement; IRBs are expected to catch and remove such language, but the responsibility to avoid it begins at the template level.

FDA Clinical Trials Database Statement

21 CFR 50.25(c), added by FDA rule in 2011, requires that applicable drug and device clinical trials include a specific statement that clinical trial information has been or will be submitted to the FDA-mandated clinical trials registry at ClinicalTrials.gov ^[14]. The template language must match the regulatory requirement precisely.

AI and Automation in ICF Development

Writing an ICF that meets regulatory requirements, reads at an accessible level, and accurately reflects the study's risk profile is time-intensive. A complex multi-arm Phase III study may require separate consent forms for screening, treatment, optional procedures, genetic substudy, and long-term follow-up, each requiring independent IRB review and version-controlled maintenance throughout the trial.

AI-assisted document generation can reduce drafting time by producing a compliant structural scaffold from protocol inputs, pre-populating required elements, and cross-referencing risk disclosures against IB content. The value is in generating a draft that already reflects the required elements and formatting conventions, so the medical writer's effort focuses on calibrating the risk language, checking benefit claims against the protocol's scientific rationale, and adapting the readability of the draft for the target population.

That said, AI tools used in ICF preparation for clinical trials must be used within a validated, governed workflow. The draft output is a starting point for human medical writing review, not a finished regulatory document. IRB review, sponsor medical monitor review, and in multi-regional trials, local regulatory authority review, remain mandatory regardless of how the draft was generated. No AI system currently has authority to certify that a consent document is compliant; that determination belongs to the IRB.

Kitsa's KScribe platform, which supports generation of regulatory and clinical documents including ICFs, is designed to produce document drafts aligned with protocol content and applicable regulatory frameworks. As with any AI-native document generation tool, human expert review and IRB approval remain required steps before any KScribe-generated ICF draft is used in a clinical investigation. No AI system has regulatory authority to certify consent form compliance; that determination belongs to the IRB under 21 CFR Part 56 ^[13].

ICF Template Checklist: Required Sections and Regulatory Basis

The table below maps each required ICF section to its regulatory basis, with notes on what FDA inspectors commonly check. Not every section applies to every study type; IRBs may require additional sections based on study-specific risk.

Key Takeaways

• Informed consent under FDA regulations requires eight basic elements under 21 CFR 50.25(a) and, when appropriate, six additional elements under 21 CFR 50.25(b); a separate ClinicalTrials.gov statement is required for applicable trials under 21 CFR 50.25(c). All eight basic elements are binding requirements for every FDA-regulated clinical investigation in which informed consent is required.
• The ICF is a living document. When new information arises during a trial, the sponsor and investigator must assess whether that information is material enough to warrant re-consent. When re-consent is required by the IRB, regulation, or protocol, the updated form must be re-executed with enrolled subjects before they continue participating.
• ICH E6(R3), finalized in January 2025 and effective in the EU as of July 23, 2025, introduces a risk-proportionate approach to consent oversight and continuing review, with expanded IRB documentation expectations including review of the consent process itself.
• eConsent is permissible under FDA's December 2016 guidance, provided the system complies with 21 CFR Part 11, as applicable, and all required elements under 21 CFR 50.25 are present; electronic format does not waive any substantive requirement.
• FDA BIMO inspection findings from clinical investigator and sponsor-investigator programs document informed consent deficiencies as a recurring observation category; individual FDA warning letters have documented failures ranging from missed consent addenda to procedures performed on subjects who had explicitly refused consent ^[1],[2],[17].
• The key information section, already required for federally funded research under the revised Common Rule, should be included in all ICF templates as a concise, plain-language opening summary; FDA has proposed adding an identical requirement to 21 CFR 50.20.
• AI tools can accelerate ICF drafting and element population, but cannot replace medical writer review, sponsor medical monitor approval, or IRB determination of compliance.

Frequently Asked Questions

References

1. [1]U.S. Food and Drug Administration. Bioresearch Monitoring (BIMO) Fiscal Year 2023 Metrics. FDA, 2024. https://www.fda.gov/media/178661/download
2. [2]U.S. Food and Drug Administration. Warning Letter: Mark S. Dacey, M.D. MARCS-CMS 722942. Center for Drug Evaluation and Research, February 2, 2026. https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/mark-s-dacey-md-722942-02022026
3. [3]U.S. Food and Drug Administration. Informed Consent: Guidance for IRBs, Clinical Investigators, and Sponsors. FDA, August 2023. https://www.fda.gov/media/88915/download
4. [4]U.S. Food and Drug Administration. 21 CFR 50.20 ; General Requirements for Informed Consent. Electronic Code of Federal Regulations. https://www.ecfr.gov/current/title-21/chapter-I/subchapter-A/part-50/subpart-B/section-50.20
5. [5]U.S. Food and Drug Administration. 21 CFR 50.25 ; Elements of Informed Consent. Electronic Code of Federal Regulations. https://www.ecfr.gov/current/title-21/chapter-I/subchapter-A/part-50/subpart-B/section-50.25
6. [6]U.S. Food and Drug Administration. 21 CFR 50.27 ; Documentation of Informed Consent. Electronic Code of Federal Regulations. https://www.ecfr.gov/current/title-21/chapter-I/subchapter-A/part-50/subpart-B/section-50.27
7. [7]International Council for Harmonisation. ICH E6(R3) Guideline for Good Clinical Practice ; Step 4 Final Guideline. ICH, January 6, 2025. https://database.ich.org/sites/default/files/ICH_E6(R3)_Step4_FinalGuideline_2025_0106.pdf
8. [8]European Medicines Agency. ICH E6(R3) Guideline for Good Clinical Practice (GCP) ; Step 5. EMA/CHMP/ICH/135/1995, adopted December 12, 2024, effective July 23, 2025. https://www.ema.europa.eu/en/documents/scientific-guideline/ich-e6-r3-guideline-good-clinical-practice-gcp-step-5_en.pdf
9. [9]OHRP and FDA. Key Information and Facilitating Understanding in Informed Consent: Draft Guidance for Sponsors, Investigators, and IRBs. HHS/FDA, March 2024. 89 FR 15094. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/key-information-and-facilitating-understanding-informed-consent-guidance-sponsors-investigators-and
10. [10]U.S. Food and Drug Administration. Protection of Human Subjects and IRBs: Proposed Rule to Harmonize 21 CFR Parts 50 and 56 with the Revised Common Rule. 87 FR 58733, September 28, 2022. https://www.federalregister.gov/documents/2022/09/28/2022-21088/protection-of-human-subjects-and-institutional-review-boards
11. [11]FDA and OHRP. Use of Electronic Informed Consent in Clinical Investigations ; Questions and Answers. FDA, December 2016. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/use-electronic-informed-consent-clinical-investigations-questions-and-answers
12. [12]International Council for Harmonisation. ICH E6(R3) Annex 2 ; Non-Traditional Clinical Trial Elements. Final version adopted June 3, 2026. https://database.ich.org/sites/default/files/ICH_E6(R3)_Annex%202_Guideline_Step%204_2026_0603_0.pdf
13. [13]U.S. Food and Drug Administration. 21 CFR Part 56 ; Institutional Review Boards. Electronic Code of Federal Regulations. https://www.ecfr.gov/current/title-21/chapter-I/subchapter-A/part-56
14. [14]U.S. Food and Drug Administration. Questions and Answers on Informed Consent Elements, 21 CFR 50.25(c). Small Entity Compliance Guide. FDA, February 2012. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/questions-and-answers-informed-consent-elements-21-cfr-ss-5025c
15. [15]U.S. Department of Health and Human Services. 45 CFR 46.116 ; General Requirements for Informed Consent (Revised Common Rule). Electronic Code of Federal Regulations. https://www.ecfr.gov/current/title-45/subtitle-A/subchapter-A/part-46/subpart-A/section-46.116
16. [16]U.S. Food and Drug Administration. 21 CFR 50.55 ; Requirements for Permission by Parents or Guardians and for Assent by Children. https://www.ecfr.gov/current/title-21/chapter-I/subchapter-A/part-50/subpart-D/section-50.55
17. [17]U.S. Food and Drug Administration. Warning Letter: Mark J. Savant, M.D. MARCS-CMS 712306. Center for Drug Evaluation and Research, June 26, 2025. https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/mark-j-savant-md-712306-06262025
18. [18]U.S. Food and Drug Administration. 21 CFR 56.109(f) ; IRB Review of Research: Continuing Review Requirement. https://www.ecfr.gov/current/title-21/chapter-I/subchapter-A/part-56/subpart-C/section-56.109
19. [19]U.S. Department of Health and Human Services. 45 CFR 46.408 ; Requirements for Permission by Parents or Guardians and for Assent by Children (Revised Common Rule). https://www.ecfr.gov/current/title-45/subtitle-A/subchapter-A/part-46/subpart-D/section-46.408